Genetic Variant NM_001136509.3:c.896G>C (chr16-31435954-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001136509.3(ZNF843):c.896G>C(p.Arg299Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000221 in 1,538,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

ZNF843
NM_001136509.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.276

Variant links:

Genes affected

ZNF843 (HGNC:28710): (zinc finger protein 843) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ZNF843 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.063877225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF843	NM_001136509.3 link	c.896G>C	p.Arg299Thr	missense_variant	Exon 2 of 2	ENST00000315678.10	NP_001129981.1	Q8N446
ZNF843	NM_001353381.1 link	c.896G>C	p.Arg299Thr	missense_variant	Exon 2 of 2		NP_001340310.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF843	ENST00000315678.10 link	c.896G>C	p.Arg299Thr	missense_variant	Exon 2 of 2	2	NM_001136509.3	ENSP00000322899.5	Q8N446
ZNF843	ENST00000618063.1 link	c.896G>C	p.Arg299Thr	missense_variant	Exon 2 of 2	1		ENSP00000483573.1	Q8N446
ZNF843	ENST00000564218.5 link	c.682+214G>C		intron_variant	Intron 2 of 2	5		ENSP00000455858.1	H3BQN5

Frequencies

GnomAD3 genomes

AF:

0.0000985

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000733

AC:

AN:

136488

Hom.:

AF XY:

0.000110

AC XY:

AN XY:

72874

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000683

Gnomad NFE exome

AF:

0.000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000234

AC:

325

AN:

1386288

Hom.:

Cov.:

AF XY:

0.000199

AC XY:

136

AN XY:

682708

show subpopulations

Gnomad4 AFR exome

AF:

0.0000639

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000208

Gnomad4 NFE exome

AF:

0.000292

Gnomad4 OTH exome

AF:

0.000157

GnomAD4 genome

AF:

0.0000984

AC:

AN:

152374

Hom.:

Cov.:

AF XY:

0.0000805

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000184

Hom.:

Bravo

AF:

0.000110

ExAC

AF:

0.0000427

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 06, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.896G>C (p.R299T) alteration is located in exon 2 (coding exon 1) of the ZNF843 gene. This alteration results from a G to C substitution at nucleotide position 896, causing the arginine (R) at amino acid position 299 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.63

CADD

Benign

7.2

DANN

Benign

0.49

DEOGEN2

Benign

0.00092

T;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.34

.;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.064

T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.0

N;N

PrimateAI

Uncertain

0.68

PROVEAN

Benign

0.44

N;.

REVEL

Benign

0.093

Sift

Pathogenic

0.0

D;.

Sift4G

Benign

0.26

T;T

Polyphen

0.94

P;P

Vest4

0.14

MVP

0.030

ClinPred

0.049

GERP RS

0.37

Varity_R

0.056

gMVP

0.042

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over